Variant rs41271312 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001384272.1(HCRTR2):c.31C>A(p.Pro11Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00718 in 1,614,056 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0059 ( 3 hom., cov: 31)

Exomes 𝑓: 0.0073 ( 46 hom. )

Consequence

HCRTR2
NM_001384272.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.807

Variant links:

Genes affected

HCRTR2 (HGNC:4849): (hypocretin receptor 2) The protein encoded by this gene is a G-protein coupled receptor involved in the regulation of feeding behavior. The encoded protein binds the hypothalamic neuropeptides orexin A and orexin B. A related gene (HCRTR1) encodes a G-protein coupled receptor that selectively binds orexin A. [provided by RefSeq, Jan 2009]

HCRTR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0064996183).

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
HCRTR2	NM_001384272.1 link	c.31C>A	p.Pro11Thr	missense_variant	1/7	ENST00000370862.4	NP_001371201.1
HCRTR2	NM_001526.5 link	c.31C>A	p.Pro11Thr	missense_variant	2/8		NP_001517.2
HCRTR2	XM_017010798.2 link	c.31C>A	p.Pro11Thr	missense_variant	2/9		XP_016866287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HCRTR2	ENST00000370862.4 link	c.31C>A	p.Pro11Thr	missense_variant	1/7	1	NM_001384272.1	ENSP00000359899.3		O43614
HCRTR2	ENST00000615358.4 link	c.31C>A	p.Pro11Thr	missense_variant	2/8	1		ENSP00000477548.1		O43614

Frequencies

GnomAD3 genomes

AF:

0.00593

AC:

902

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00152

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0107

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00919

Gnomad OTH

AF:

0.00623

GnomAD3 exomes

AF:

0.00486

AC:

1223

AN:

251400

Hom.:

AF XY:

0.00468

AC XY:

636

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00520

Gnomad ASJ exome

AF:

0.00318

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000653

Gnomad FIN exome

AF:

0.00148

Gnomad NFE exome

AF:

0.00789

Gnomad OTH exome

AF:

0.00684

GnomAD4 exome

AF:

0.00731

AC:

10684

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00698

AC XY:

5077

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00185

Gnomad4 AMR exome

AF:

0.00514

Gnomad4 ASJ exome

AF:

0.00341

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000614

Gnomad4 FIN exome

AF:

0.00182

Gnomad4 NFE exome

AF:

0.00874

Gnomad4 OTH exome

AF:

0.00695

GnomAD4 genome

AF:

0.00593

AC:

902

AN:

152202

Hom.:

Cov.:

AF XY:

0.00555

AC XY:

413

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.00152

Gnomad4 AMR

AF:

0.0107

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.00919

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00726

Hom.:

Bravo

AF:

0.00580

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.00960

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00756

AC:

ExAC

AF:

0.00463

AC:

562

EpiCase

AF:

0.00747

EpiControl

AF:

0.00688

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.16

T;T

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.80

T;.

MetaRNN

Benign

0.0065

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;L

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.19

.;N

REVEL

Benign

0.26

Sift

Benign

0.072

.;T

Sift4G

Benign

0.39

T;T

Polyphen

0.035

B;B

Vest4

0.76

MVP

0.66

MPC

0.44

ClinPred

0.0058

GERP RS

3.1

Varity_R

0.052

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over